Effects of maternal exposure to arsenic on social behavior and related gene expression in F2 male mice

BACKGROUND@#Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice.@*METHODS@#Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method.@*RESULTS@#The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice.@*CONCLUSIONS@#These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.

Melatonin protective role in mouse cauda epipidymal spermatozoa damage induced by sodium arsenite / Rol protector de la melatonina en el daño de espermatozoides de cauda epididimaria en ratón producido por arsenito de sodio

We evaluated the sperm parameters such as cauda epididymis weight, sperm count, sperm morphology and sperm DNA stability of adult CF-1 male mice treated daily (oral exposure) with the toxic sodium arsenite (As, 7.0 mg/kg/body weight); Melatonin (Me, 10.0 mg/kg/bw), Me (10.0 mg/kg/bw) plus As (7.0 mg/kg/bw) and Negative Control (NaCl 0.9 percent) to assess acute (8.3 days), chronic (33.2 days) and recovery of testicular damage (66.4 days). Arsenic decreases the number of sperm from chronic treatment (33.2 days) and this effect continued until 66.4 days of treatment. The toxic effect of As also altered the morphology of spermatozoa in all treatment periods when compared to the negative control group. However, Metalonin induced protective effects in periods of 33.2 and 66.4 days of treatment. Additionally, the stability of DNA was significantly affected by arsenic in all periods, but the chronic treatment (33.2 days) in the AsMe revealed increased stability compared to the group treated with arsenic only. Melatonin partially protects sperm toxicity caused by Arsenic, especially during periods of 33.2 and 66.4 days.

Se evaluaron los parámetros espermáticos como peso de la cola del epidídimo, conteo de espermatozoides, morfología de los espermatozoides y estabilidad del ADN de espermatozoides de ratones machos adultos CF-1 tratados diariamente (exposición oral) con el tóxico arsenito de sodio (As, 7,0 mg/kg/peso corporal), melatonina (Me, 10,0 mg/kg/pc, Me (10,0 mg/kg/pc) más As (7,0 mg/kg/pc) y el Control Negativo (NaCl 0,9 por ciento) en evaluación aguda (8,3 días), crónica (33,2 días) y recuperación del daño testicular (66.4 días). El arsénico reduce el número de espermatozoides en el tratamiento crónico (33,2 días) y este efecto continuó hasta 66,4 días. El efecto tóxico de As también altero la morfología de los espermatozoides en todos los períodos de tratamiento cuando se compara con el grupo control negativo. Sin embargo, metalonina indujo efectos protectores en períodos de 33,2 y 66,4 días de tratamiento. La estabilidad del ADN se vio afectada significativamente por el arsénico en todos los periodos, pero en el tratamiento crónico (33,2 días) con AsMe se observa un aumento de la estabilidad em comparación com el grupo tratado con arsénico. Sin embargo, la melatonina protege parcialmente a los espermatozoides del daño causado por arsénico, especialmente durante los períodos de 33,2 y 66,4 días.

Acute Kidney Injury due to Sodium Bromate Intoxication: A Report of Two Cases

Sodium bromate is a strong oxidant used as a neutralizing solution in hair permanents, as well as an auxiliary agent in printing and dyeing. Accidental or deliberate ingestion of bromate solution has rarely been reported in Korea. The clinical manifestations of bromate intoxication are vomiting, diarrhea, central nervous system symptoms, oliguric or non-oliguric acute kidney injury, hemolytic anemia, and deafness; most of these manifestations are reversible, with the exception of renal failure and deafness. Here, we report on two patients who demonstrated distinct clinical progressions. In the first case, a 16-year-old woman was successfully treated with hemodialysis and recovered renal function without hearing loss. However, in the second case, delayed hemodialysis resulted in persistent renal failure and hearing loss in a 77-year-old woman. This suggests that emergency therapeutic measures, including hemodialysis, should be taken as soon as possible, as the rapid removal of bromate may be essential to preventing severe intoxication and its sequelae.

Arsenic induced toxicity on testicular tissue of mice.

Effect of arsenic was studied on the testicular tissue of Swiss albino mice. Sodium-meta-arsenite (NaAsO2) was administered to adult mice (25 +/- 30 g) at a dose level of 30 mg/L and 40 mg/L through drinking water for 30, 45 and 60 days. After the treatment, the testicular organ was removed, weighed and processed for histopathological observation. No change in the body weight was recorded in treated groups after arsenic exposure but significant decrease in the relative testicular weight was observed in comparison with the control. The result showed that arsenic-treated mice exhibited dose dependent gradual reductions in seminiferous tubular diameter and various gametogenic cell population i.e. resting spermatocyte, pachytene spermatocyte and step-7-spermatid except spermatogonia. Leydig cell atrophy was significantly increased in dose dependent manner indicating a definite effect of arsenic on the spermatogenesis in mice. These observations were supported by gradual reduction in Leydig cell population in the above treated groups. In conclusion, the above results confirm the toxic effect of arsenic in testis of mice.

[Quantitative study of the histopathological effects of sodium arsenite on kidney stracture in rats]

Sodium arsenite is an environmental pollutant which its amounts in industrial cities are more than other places because of its use in chemical industry. Human populations are exposed to this chemical compound through food, soil, air and water which has toxic and histopathological effects on different body organs including kidney. The aim of this investigation is to study the quantitative histopathological effects of sodium arsenite on the kidney structure of rats. 12 male Wistar rats with mean body weight of 200 +/- 20 g were randomly divided into 2 groups [n=6]. One treated with sodium arsenite [8 mg/kg/day in drinking water] and the other one [the control group] received drinking water only. 2 months after treatment the rats were weighed, anesthetized with ether and dissected. The left kidney was taken out, cleaned, weighed and then fixed in 10% formaldehyde solution. After obtaining 1mm thick slices, tissue processing was carried out, then 5 micro m thick sections were prepared and stained using H and E method. Slides were finally studied stereologically and data was statistically analyzed using paired samples t-test and the means were considered significantly different at p<0.05. The results of this investigation indicated significant reduction in the total mean volume of kidney [p<0.001] and cortex [p<0.001] and medulla [p<0.003] in sodium arsenite treated group compared to the control rats. The mean volume of tubules and interstitial tissue as components of cortex reduced significantly compared to the control group [p<0.003].The mean volume of glomeruli and Bowman's capsule significantly reduced in treated group [p<0.001]. While the other components did not show a significant reduction in volume. A significant reduction was also found in the kidney [p<0.002] and the body weight [p<0.01] in the treated group compared to the control ones at the end of the experiment. We concluded that exposure to sodium arsenite leads to histopathological changes in kidney structure however more studies are needed to determine the effects of these structural changes on the kidney function

In vitro induction of abnormal anaphases by contaminating atmospheric dust from the city of Mexicali, Baja California, Mexico

Mexicali dust (MD) is a mixture of particles of potassium aluminum silicates (98 percent) and sodium dioxide (2 percent) that induces pulmonary damage under experimental conditions, and is capable of inducing in vitro chromosomal alterations in exposed lymphocytes. It has been proposed as an atmospheric contaminant with pathogenic potential. among the chromosomal alterations observed, numeric alterations were predominant. The present study was designed to evaluate the capacity of MD to induce anaphasic changes in the Balb c 3T3 cell line. Chrysotile asbestos was used as a positive control. MD was found to induce abnormal anaphases, and the percentage of abnormalities increased as the dose increased (27.41 percent with 20 mg/mL, 29.60 percent with 40 mg/mL and 37.10 percent with 80 mg/mL). Multipolar anaphases constituted the most frequent altertion (69.1 - 78.8 percent), followed by lagging chromosomes (18.2 -29.5 percent) and anaphasic bridges (1.51 - 5.9 percent). The anaphasic alterations induced by MD showed differences in comparison to those observed with asbestos, especially for anaphasic bridges (10.4 percent vs. 1.51 percent, p<0.05). The capacity of MD to induce alterations resported in the process of chromosomal disjunction could explain the numeric aberrations reported previously by the authors of this paper. Therefore, these data support that MD could act as a clastogenic agent